Abstract

4817

Development of small molecules for protection from irradiation by irradiation spills, or radiological terrorism requires need for low toxicity and administration proximate to time of irradiation. We have tested the dietary component resveratrol and an acetylated moiety of resveratrol with increased stability. Mouse hematopoietic progenitor 32D cl 3 cells were incubated for 1 hour in 10 µM resveratrol, acetylated resveratrol or control medium, then irradiated at doses ranging from 0 to 8 Gy, plated in 0.8% methycellulose, and incubated in a 5% CO2 incubator for 7 days. Colonies of greater than 50 cells were counted and the data analyzed using Linear Quadratic or Single-Hit, Multi-Target Models. Incubation of 32D cl 3 cells in resveratrol or acetylated resveratrol before irradiation resulted in an increased shoulder on the survival curve of 33.2 + 5.7 or 57.5 + 9.9, respectively, compared to 6.9 + 1.8 for 32D cl 3 cells (p = 0.0122 or 0.0072, respectively). To determine if these compounds were radioprotective in vivo against an LD50/30 irradiation dose, C57BL/6NHsd female mice were injected intraperitoneally with 0, 1.0, 10, or 25 mg/kg of resveratrol or acetylated resveratrol and irradiated 10 min later along with control mice to 9.75 Gy whole body irradiation. The mice injected with acetylated-resveratrol had increased survival at 10 and 25 mg/kg compared to control irradiated mice (p < 0.0001 or = 0.0004, respectively). However, resveratrol resulted in no significant increase in survival. Neither resveratrol nor acetylated resveratrol were effective if given after irradiation. Thus acetylated resveratrol is a potentially effective radioprotector.